Rational: Social deficits are disabling, treatment refractory symptoms of schizophrenia. The amygdala is thought to modulate this behavior, and disruption of NMDA receptor (NMDAR) mediated glutamate transmission has been implicated as well. However, a detailed understanding of the cellular and regional circuit mechanisms underlying social deficits is lacking. Hypotheses: We propose that disrupted development and functioning of glutamatergic inputs to NMDARs on basolateral amygdala (BLA) neurons can disrupt acquisition and maintenance of normal social behavior. Furthermore, increased resting activity, i.e. noise, in BLA leads to disruption of normal signal processing and reduced signal-to-noise ratio (SNR) for social inputs from cortico-limbic brain regions. Approach: We will use in vivo electroencephalography, local field potentials (LFP) and multiunit recording in in BLA and hippocampus during social behavior as well as voltage sensitive dye imaging (VSDI) and intracellular recordings in slices from mice with disrupted NMDAR signaling. Model systems will include mice with constitutive reduction in NMDAR1 expression (NRl-/-) that have deficits in EEG and social interactions, as well as mice with amygdala-selective reduction in NRl using NRIflox mice with AAV-Cre injections. Interpretation: Data will inform interpretation of regional brain activation using fMRI and surface EEG (Project 1) in schizophrenia and at risk subjects. We will also examine novel pharmacologic approaches for restoration of excitatory-inhibitory balance in BLA at rest and during social behaviors. Public Welfare Statement: People with schizophrenia have difficulty in social interactions, which is disabling and resistant to current treatments. A part of the brain called the amygdala is thought to modulate normal social interactions, and disruption of the neurotransmitter glutamate at a receptor called the NMDA receptor, has been implicated in causing problems with normal social interactions in schizophrenia. This project will determine if disruption of glutamate activity at NMDA receptors in amygdala in mice can cause social deficits, and if fixing that activity with new medications could restore normal social function .